The pituitary tumour‐transforming gene 1/delta‐like homologue 1 pathway plays a key role in liver fibrogenesis

Autor: Meritxell Perramón, Silvia Carvajal, Vedrana Reichenbach, Guillermo Fernández‐Varo, Loreto Boix, Laura Macias‐Muñoz, Pedro Melgar‐Lesmes, Jordi Bruix, Shlomo Melmed, Santiago Lamas, Wladimiro Jiménez
Rok vydání: 2022
Předmět:
Zdroj: Liver International. 42:651-662
ISSN: 1478-3231
1478-3223
DOI: 10.1111/liv.15165
Popis: PTTG1 is almost undetectable in adult livers but is highly expressed in hepatocarcinoma. While little is known about its involvement in liver fibrosis, PTTG1 expression is associated with DLK1. We assessed the role of the PTTG1/DLK1 pathway in fibrosis progression and the potential therapeutic effect of PTTG1 silencing in fibrosis.Pttg1 and Dlk1 were studied in liver and isolated cell populations of control and fibrotic rats and in human liver biopsies. The fibrotic molecular signature was analysed in Pttg1Pttg1 and Dlk1 mRNA selectively increased in fibrotic rats paralleling fibrosis progression. Serum DLK1 concentrations correlated with hepatic collagen content and systemic and portal haemodynamics. Human cirrhotic livers showed greater PTTG1 and DLK1 transcript abundance than non-cirrhotic, and reduced collagen was observed in Pttg1 Pttg1Pttg1/Dlk1 are selectively overexpressed in the cirrhotic liver and participate in ECM turnover regulation. Pttg1 disruption decreases Dlk1 transcription and attenuates collagen deposition. PTTG1/DLK1 signalling is a novel pathway for targeting the progression of liver fibrosis.
Databáze: OpenAIRE
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